scholarly journals Efficacy of the Aqueous Extract of Azadirachta indica Against the Marine Parasitic Leech and Its Phytochemical Profiling

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1908
Author(s):  
Balu Alagar Venmathi Maran ◽  
Dawglas Josmeh ◽  
Jen Kit Tan ◽  
Yoong Soon Yong ◽  
Muhammad Dawood Shah
Keyword(s):  
Mass Spectrometry ◽  
Aqueous Extract ◽  
Azadirachta Indica ◽  
Total Mortality ◽  
Mass Spectrometry Analysis ◽  
Economic Losses ◽  
Dependent Manner ◽  
Spectrometry Analysis ◽  
Orbitrap Mass Spectrometry ◽  
Q Exactive

Zeylanicobdella arugamensis (Hirudinea), a marine parasitic leech, not only resulted in the mortality of the host fish (Groupers) but also caused economic losses. The current study aimed to elucidate the antiparasitic efficacy of the aqueous extract of the Azadirachta indica leaves against Z. arugamensis and to profile the composition via LC-Q Exactive HF Orbitrap mass spectrometry. Different concentrations (25, 50 and 100 mg/mL) of A. indica extract were prepared and tested on the parasitic leeches. The total mortality of leeches was noticed with an exposure to the A. indica aqueous extract. The average times required for the aqueous extract at concentrations of 25, 50 and 100 mg/mL to kill the leeches were 42.65 ± 9.20, 11.69 ± 1.11 and 6.45 ± 0.45 min, respectively, in a dose-dependent manner. The Orbitrap mass spectrometry analysis indicated the presence of five flavonoids (myricetin 3-O-galactoside, trifolin, isorhamnetin, quercetin and kaempferol), four aromatics (4-methoxy benzaldehyde, scopoletin, indole-3-acrylic acid and 2,4-quinolinediol), three phenolics (p-coumaric acid, ferulic acid and phloretin) and two terpenoids (pulegone and caryophyllene oxide). Thus, our study indicates that A. indica aqueous extract is a good source of metabolites with the potential to act as a biocontrol agent against the marine parasitic leech in aquaculture.

scholarly journals Rapid Identification of 3,6′-Disinapoyl Sucrose Metabolites in Alzheimer’s Disease Model Mice Using UHPLC–Orbitrap Mass Spectrometry

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 114
Author(s):  
Jiaqi Yuan ◽  
Han Wang ◽  
Yunting Wang ◽  
Zijian Wang ◽  
Qing Huo ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Bond Cleavage ◽  
Disease Model ◽  
Sinapic Acid ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
Orbitrap Mass Spectrometry

Alzheimer’s disease (AD) is a degenerative disease of the central nervous system characterized by the progressive impairment of neural activity. Studies have shown that 3,6′-disinapoyl sucrose (DISS) can alleviate the pathological symptoms of AD through the activation of the cAMP/CREB/BDNF signaling pathway. However, the exact biochemical mechanisms of action of DISS are not clear. This study explores metabolism of DISS in an AD mouse model, induced by the microinjection of a lentiviral expression plasmid of the APPswe695 gene into CA1 of the hippocampus. After gavage administration of DISS (200 mg/kg), the kidneys, livers, brains, plasma, urine, and feces were collected for UHPLC–Orbitrap mass spectrometry analysis. Twenty metabolites, including the prototype drug of DISS, were positively or tentatively identified based on accurate mass measurements, characteristic fragmentation behaviors, and retention times. Thus, the metabolic pathways of DISS in AD mice were preliminarily elucidated through the identification of metabolites, such as ester bond cleavage, demethoxylation, demethylation, and sinapic acid-related products. Furthermore, differences in the in vivo distribution of several metabolites were observed between the model and sham control groups. These findings can provide a valuable reference for the pharmacological mechanisms and biosafety of DISS.

scholarly journals Effect of Cadmium on the Level of Isoprenoid-Derived Phytohormones in Duckweed Wolffia arrhiza

2020 ◽  
Vol 39 (4) ◽  
pp. 1518-1530
Author(s):  
Magdalena Chmur ◽  
Andrzej Bajguz ◽  
Alicja Piotrowska-Niczyporuk
Keyword(s):  
Mass Spectrometry ◽  
Aquatic Plant ◽  
Mass Spectrometry Analysis ◽  
Dependent Manner ◽  
Spectrometry Analysis ◽  
Flight Mass Spectrometry ◽  
Endogenous Level ◽  
Wolffia Arrhiza ◽  
First Time ◽  
Dose Dependent

AbstractWolffia arrhiza (L.) Horkel ex Wimm. is an aquatic plant belonging to the Lemnaceae family. It does not have leaves, stems, and roots, flowers rarely occur, while body size can reach 1 mm of width and 1.3 mm of length. The present study demonstrates the endogenous level of isoprenoid-derived phytohormones and their changes under the influence of different cadmium (Cd) concentrations (0.1, 1, 10, and 100 µM). A liquid chromatography quadrupole-time-of-flight mass spectrometry analysis indicated the presence of abscisic acid, eight brassinosteroids (6-deoxocastasterone, 6-deoxotyphasterol, cathasterone, typhasterol, castasterone, 24-epicastasterone, brassinolide, and 28-homobrassinolide), seven free bases of cytokinins [trans-zeatin (tZ), cis-zeatin (cZ), dihydrozeatin (DHZ), N6-isopentenyladenine, N6-isopentenyladenosine, ortho-topolin, and meta-topolin], eight conjugates of cytokinins (tZ riboside, tZ-9-glucoside, tZ-7-glucoside, tZ-O-glucoside riboside, cZ-9-glucoside, DHZ riboside, DHZ-O-glucoside, and N6-isopentenyladenosine-7-glucoside) and gibberellic acid (GA3) in this duckweed. The level of phytohormones in plants treated with Cd has changed, e.g., the ABA level increased while GA3 decreased. Whereas the amount of BRs and CKs was different in Cd dose-dependent manner. Besides, it is worth noting that the distribution of 25 various phytohormones in the Wolffia arrhiza is reported for the first time.

scholarly journals Phenolic Profile of Grape Canes: Novel Compounds Identified by LC-ESI-LTQ-Orbitrap-MS

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3763 ◽  
Author(s):  
Saéz ◽  
Riquelme ◽  
Baer ◽  
Vallverdú-Queralt
Keyword(s):  
Mass Spectrometry ◽  
High Resolution Mass Spectrometry ◽  
Mass Spectrometry Analysis ◽  
Vitis Vinifera L ◽  
Economic Potential ◽  
Phenolic Profile ◽  
Spectrometry Analysis ◽  
Orbitrap Mass Spectrometry ◽  
Fragmentation Patterns ◽  
Polyphenolic Profile

Grape canes (Vitis vinifera L.) are a viticulture industry by-product with an important content of secondary metabolites, mainly polyphenols with a broad spectrum of demonstrated health benefits. Grape canes, therefore, have considerable economic potential as a source of high-value phytochemicals. In this work, liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole-Orbitrap mass spectrometry (LC–LTQ-Orbitrap) was used for the comprehensive identification of polyphenolic compounds in grape canes. Identification of polyphenols was performed by comparing their retention times, accurate mass measured, and mass fragmentation patterns with those of reference substances or available data in the literature. A total of 75 compounds were identified, including phenolic acids, flavanols, flavonols, flavanonols, flavanones, and stilbenoids. The most abundant polyphenols were proanthocyanidins and stilbenoids and their oligomers. Moreover, the high-resolution mass spectrometry analysis revealed the occurrence of 17 polyphenols never described before in grape canes, thereby providing a more complete polyphenolic profile of this potentially valuable by-product.

scholarly journals Identification of Thrombospondin-1 As a Novel Substrate of Cereblon Responsible for IMiDs-Induced Venous Thromboembolism

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 631-631
Author(s):  
Kiwamu Hatakeyama ◽  
Yoshikane Kikushige ◽  
Toshihiro Miyamoto ◽  
Koichi Akashi
Keyword(s):  
Mass Spectrometry ◽  
Venous Thromboembolism ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Leukemia Cell ◽  
Mass Spectrometry Analysis ◽  
Leukemia Cell Line ◽  
Dependent Manner ◽  
Hematopoietic Stem ◽  
Spectrometry Analysis

Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide, are key drugs for the treatment of multiple myeloma (MM) and myelodysplastic syndrome(MDS) with chromosome 5q deletion[del(5q)].IMiDs modulate the ubiquitination of intracellular proteins by E3 ubiquitin ligase and alter the stability of target proteins via proteasomal degradation. IMiDs directly bind to cereblon (CRBN), a substrate receptor for the E3 ubiquitin ligase complex, and retarget the enzyme complex toward neo-substrates such as IKAROS family zinc finger 1/3 (IKZF1/3) and casein kinase 1α (CK1α) in MM and MDS with del(5q), respectively, which underlies their clinical efficacy in these disorders. Thus, the identification of cell specific neo-substrates should be a critical step to understand IMiDs-mediated pleiotropic effects. Clinically, IMiDs cause venous thromboembolism (VTE); however, the molecular machineries how IMiDs increase the risk of VTE still remains elusive. We, therefore, hypothesized that there is an unknown substrate for CRBN that induces thrombosis in megakaryocytes and platelets. To identify possible molecules that could interact with CRBN in human megakaryocytes, we performed screening analysis. Human CD34+hematopoietic stem/progenitor cells (HSPCs) from cord blood were cultured in a serum-free megakaryocytic condition for 7 days as previously reported. Most of the CD34+HSPCs were differentiated into CD41+CD42b+mature megakaryocytes, and we extracted human megakaryocytic protein. Cellular lysates from CD34+HSPCs-derived megakaryocytes and FLAG-tagged CRBN-overexpressing HEK293T cells were mixed with or without lenalidomide. CRBN-binding proteins were subsequently pulled down using anti-FLAG antibody, and subjected to mass spectrometry analysis. Mass spectrometry analysis revealed that THBS1 was coimmunoprecipitated with CRBN, and its interaction was decreased in the presence of lenalidomide. We therefore hypothesized that THBS1 could be a neo-substrate for CRBN. Consistent with the screening results, we found that IMiDs increased THBS1 protein in Meg-01 cells, a human megakaryoblastic leukemia cell line in a dose and time dependent manner, without affecting mRNA level. Proteasome inhibitor increased THBS1 level in Meg-01 cells, suggesting that THBS1 should be physiologically degraded via proteasome. The immunoprecipitation experiments showed CRBN and THBS1 conjugation, which was inhibited in the presence of Lenalidomide in vitro. Furthermore, we confirmed an increase in THBS1 protein level in the bone marrow and plasma of MM patients treated with IMiDs-containing regimen, suggesting that IMiDs actually induce the accumulation of THBS1 in vivo. These results collectively suggest that THBS1 is a neo-substrate for CRBN and IMiDs induces the accumulation of THBS1 through the inhibition of proteasomal THBS1 degradation in human. THBS1 is reported to competitively inhibit ADAMTS13 activity of von Willebrand Factor (vWF) multimer cleavage, leading to increased level of large vWF multimers. Since large vWF multimers promote thrombus formation and several studies showed increased plasma level of THBS1 correlates with the incidence of VTE, we tested whether the accumulation of THBS1 induced by IMiDs treatment could affect the size of vWF multimer in MM patients. vWF multimer analysis revealed the large vWF multimers increased in plasma of MM patients undergoing IMiDs treatment. These results collectively suggest that IMiDs-induced accumulation of THBS1 should be one of the molecular machineries for IMiDs-induced VTE in human. Disclosures Akashi: Celgene, Kyowa Kirin, Astellas, Shionogi, Asahi Kasei, Chugai, Bristol-Myers Squibb: Research Funding; Sumitomo Dainippon, Kyowa Kirin: Consultancy.

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